Pathophysiology: Organism has a predilection for endothelial cells, leading to widespread vasculitis, increased vascular permeability, edema, and organ damage.
Clinical Features
Sudden high fever, severe headache, myalgias, GI Sx (nausea, pain).
Dx is primarily clinical. Do not delay treatment awaiting confirmation.
Labs (nonspecific but classic associations):
Thrombocytopenia (due to endothelial damage and platelet consumption) c
Hyponatremia (due to Increased vascular permeability causes intravascular fluid, sodium, and albumin to leak into interstitial spaces → ADH secretion) c
↑ LFTs
Confirmatory Tests:
Gold Standard: Indirect immunofluorescence assay (IFA) for IgM/IgG antibodies. Titers do not rise until 7-10 days into illness (retrospective).
Skin biopsy of rash with immunohistochemical (IHC) staining.
CSF Analysis (indicated if meningismus or altered mental status is present):
Opening Pressure: Normal or mildly elevated.
WBC / Cell Count: Mild pleocytosis (typically < 100–500 cells/µL) with lymphocytic or neutrophilic predominance.
Protein: Mildly to moderately elevated (microvascular endothelial leak/blood-brain barrier disruption).
Glucose: Normal (rarely mildly low).
Gram Stain: Negative (obligate intracellular organism; poorly visualizable on standard Gram stain).
Differential diagnostics
Ehrlichiosis/Anaplasmosis: Similar labs, rash is rare in adults; (+) morulae on blood smear.
Meningococcemia: Rapid progression (in 12-24 hrs), rash starts on trunk, (+) CSF Gram-neg diplococci. c
Lyme Disease: Erythema migrans (bullseye lesion), no petechial rash or severe hyponatremia.
Treatment
First-line for ALL patients (including children <8 and pregnant women): Doxycycline.
The risk of mortality from untreated RMSF far outweighs the minimal risk of dental staining from a short course of doxycycline in children.
Dx: Primarily clinical, confirmed with serology (indirect immunofluorescence assay). Weil-Felix test is historical but may appear on exams.
Tx: Doxycycline for all types, including in children.
Epidemic Typhus
Etiology
Rickettsia prowazekii
Transmission
Vector: Human body louse (Pediculus humanus corporis)
Reservoir: Humans
Associated with poor hygiene, crowding (war, famine, refugee camps).
Rare US reservoir: Flying squirrels.
Clinical Features
Abrupt onset of high fever, severe headache, confusion, myalgias.
Rash appears ~5 days after fever: Maculopapular rash that starts on the trunk/axilla and spreads centrifugally to extremities, characteristically SPARING the face, palms, and soles.
Complications
Myocarditis, delirium, coma, gangrene.
Brill-Zinsser disease: Recrudescent form of epidemic typhus that can occur years after the primary infection.
Endemic (Murine) Typhus
Etiology
Rickettsia typhi
Transmission
Vector: Rat flea (Xenopsylla cheopis)
Reservoir: Rodents (rats)
Clinical Features
Milder than epidemic typhus.
Gradual onset of fever, headache, myalgias.
Rash is less common (<50% of pts) and less severe; typically maculopapular on the trunk.
Scrub Typhus
Etiology
Orientia tsutsugamushi (Note: Not a Rickettsia genus, but clinically similar).
Transmission
Vector: Chiggers (larval mites).
Reservoir: Rodents. Common in Asia, Australia, Pacific Islands.
Clinical Features
Fever, headache, myalgias.
Key Finding: Painless eschar (dark, crusted lesion) at the site of the chigger bite is pathognomonic.